The long-term objective of this project is to understand quantitatively the mechanism of alpha-helix formation by peptides in water. This means being able to predict for any peptide the amount of helix that is formed by a given amino acid sequence. The health-related significance of this work is to understand the mechanism of protein folding, which is one of the most basic problems in biomedical research. The study of alpha-helix formation represents the analysis of protein folding at its simplest and most fundamental level. Exact physico-chemical answers can be obtained to questions asked about the mechanism of folding. The main determinants of peptide helix formation are known to be the helix and N-cap propensities of the 20 amino acids and the helix-stabilizing interactions that occur between specific pairs of side chains. Rapid progress has been made recently in measuring helix and N-cap propensities of the 20 amino acids in water. The specific aims of this proposal are as follows. First, to measure these parameters in trifluoroethanol-water mixtures, for comparison with values determined in water, to help take account of the fact that helices in proteins are half exposed to water and half buried, out of contact with water. Second, to synthesize peptides whose sequences correspond to helical regions in proteins, and to compare the predicted and observed helix contents of these peptides. Third, to measure two classes of helix- stabilizing side-chain interactions: hydrogen bonds formed by specific pairs of side chains, and hydrophobic interactions formed by various pairs of nonpolar chains.